Fixation of tissue samples with formalin and paraffin is an established approach for long-term storage of tissues for later histological analyses. These formalin-fixed paraffin-embedded tissues can also be used for DNA, RNA or protein extraction for retrospective molecular studies. Unfortunately, traditional preservation methods do not guarantee uniform fixation, frequently resulting in excessive cross-linking of molecules on the periphery of the specimen and slow degradation in its depth. Consequently, antigen retrieval, genomic or proteomic biomarker identification studies may generate inaccurate or misleading results. Attempts at alternative fixation methods, such as convectional heat or microwave radiation treatment, have also proven inadequate, since they fail to produce a uniform product, or result in perturbations to the biomolecular profiles. We propose to develop an automated tissue preservation system that uses high hydrostatic pressure to standardize the process of tissue fixation with precise thermodynamic control. High pressure has been shown to enhance rapid and uniform formaldehyde penetration into tissue blocks. The proposed Tissue Preservation System will enable better preservation of tissues through enhanced penetration of fixative while preserving tissue architecture. Such improvements should lead to the generation of better data from preserved samples, which may lead to faster disease diagnosis and successful development of therapeutics. 1 PUBLIC HEALTH RELEVANCE: The proposed study aims to develop a high pressure system for automated preservation of clinical tissue specimens to facilitate and standardize the tissue fixation process independent of specimen size and tissue type. Better, more consistent, and more uniform preservation of tissue architecture, and improved chemical integrity of potential biomarkers, are expected to lead to considerable benefits for future histopathology and retrospective molecular diagnostics studies using fixed sample repositories.